RT Journal Article SR Electronic T1 The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.09.434607 DO 10.1101/2021.03.09.434607 A1 Andrea L. Cathcart A1 Colin Havenar-Daughton A1 Florian A. Lempp A1 Daphne Ma A1 Michael A. Schmid A1 Maria L. Agostini A1 Barbara Guarino A1 Julia Di iulio A1 Laura E. Rosen A1 Heather Tucker A1 Joshua Dillen A1 Sambhavi Subramanian A1 Barbara Sloan A1 Siro Bianchi A1 Dora Pinto A1 Christian Saliba A1 Katja Culap A1 Jason A Wojcechowskyj A1 Julia Noack A1 Jiayi Zhou A1 Hannah Kaiser A1 Arthur Chase A1 Martin Montiel-Ruiz A1 Exequiel Dellota, Jr. A1 Arnold Park A1 Roberto Spreafico A1 Anna Sahakyan A1 Elvin J. Lauron A1 Nadine Czudnochowski A1 Elisabetta Cameroni A1 Sarah Ledoux A1 Adam Werts A1 Christophe Colas A1 Leah Soriaga A1 Amalio Telenti A1 Lisa A. Purcell A1 Seungmin Hwang A1 Gyorgy Snell A1 Herbert W. Virgin A1 Davide Corti A1 Christy M. Hebner YR 2022 UL http://biorxiv.org/content/early/2022/02/18/2021.03.09.434607.abstract AB Sotrovimab (VIR-7831) and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sotrovimab and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) survivor. Both mAbs contain an “LS” mutation in the Fc region to prolong serum half-life. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection. Sotrovimab and VIR-7832 potently neutralize wild-type and variant pseudotyped viruses and authentic virus in vitro. In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to previously authorized mAbs. The sotrovimab/VIR-7832 epitope continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept wildtype SARS-CoV-2 infection model, animals treated with sotrovimab had less weight loss, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that sotrovimab and VIR-7832 are key agents in the fight against COVID-19.Competing Interest StatementSome authors are current or former employees of Vir Biotechnology or Humabs BioMed SA (a fully-owned subsidiary of Vir Biotechnology) and may hold shares in Vir Biotechnology. H.W.V. is a founder of PierianDx and Casma Therapeutics.